Short-term modulation of the ipsilateral primary sensory cortex by nociceptive interference revealed by SEPs.

We studied the modulation of the topographic arrangement of the human ipsilateral primary somatosensory cortex following interference of nociceptive stimuli by means of dipole source analysis. Multichannel somatosensory evoked potentials were obtained by electrical stimulation of digits 1 and 5 of the left hand before, during and after the application of pain to digits 2-4 of the right hand. The primary cortical response of the SEP (N20) was obtained for dipole localization of the representation of the primary sensory cortex receiving input from digits 1 to 5. The 3D-distance between these sides was calculated for further analysis. To account for possible attentional effects recordings were performed while simultaneously to this intervention subjects were asked to turn their attention to the right or left hand in a pseudorandom order. The application of pain induced an expansion of the 3D-distance between digits 1 and 5. Focusing attention to the stimulated limb or the site of the intervention did not yield to an additional effect. Our results provide further evidence for the presence of a quickly adapting interaction between primary somatosensory areas of both hemispheres following an interference of nociceptive stimulation in SEPs. This modifying process is probably mediated by interhemispheric and intercortical connections leading to hyperexcitability of the primary sensory cortex contralateral to that receiving nociceptive input. Spatial attention does not seem to have an impact on this kind of short-term intercortical plasticity.

Interference of tactile and pain stimuli on thalamocortical signal processing in humans revealed by median nerve SEPs.

OBJECTIVE: We investigated the interference of tactile and painful stimuli on human early somatosensory evoked potentials (SEPs) including high frequency oscillations (HFOs) to further study thalamocortical processing of somatosensory information. METHODS: Multi-channel median nerve SEPs were recorded during (1) no interference, (2) sensory interference by tactile stimulation to digits 2 and 3, and (3) application of pain to the same digits. Spatio-temporal source analysis separated brain stem (S1), thalamic (S2) and two cortical sources (S3, S4), which were evaluated for the low (20-450 Hz) and high (450-750 Hz) frequency portion of the signal. RESULTS: Low frequency SEPs showed a decrease of activity at cortical source S3 during both conditions, while thalamic source S2 was significantly increased during pain interference. HFOs showed an increase of cortical source S3 and in trend of thalamic source S2 and cortical source S4 during both kinds of interference. CONCLUSIONS: Although the painful stimulus might not be specific for the nociceptive afferents, the present data affirm that at this early stage of sensory information processing within the primary sensory cortex (area 3b, area 1) pain is handled similar to sensory interference. SIGNIFICANCE: HFOs might represent an intrinsic "somatosensory alerting" system which reacts to both interference stimuli in a similar way, therefore indicating an interference without a qualitative evaluation.

Different origins of low- and high-frequency components (600 Hz) of human somatosensory evoked potentials.

OBJECTIVE: Human median nerve somatosensory evoked potentials (SEPs) contain a low-amplitude (<500 nV) high-frequency (approximately 600 Hz) burst of repetitive wavelets (HFOs) which are superimposed onto the primary cortical response 'N20.' This study aimed to further clarify the cortical and subcortical structures involved in the generation of the HFOs. METHODS: 128-Channel recordings were obtained to right median nerve stimulation of 10 right-handed healthy human subjects and in 7 of them additional to right ulnar nerve. Data were evaluated by applying principal component analysis and dipole source analysis. RESULTS: Different source evaluation strategies provided converging evidence for a cortical HFO origin, with two different almost orthogonally oriented generators being active in parallel, but with a phase shift of a quarter of their oscillatory period, while the low-frequency 'N20' is adequately modeled by one tangential dipole source. Median and ulnar derived low-frequency and HFO cortical sources show a somatotopic order. Additionally, generation of the HFOs was localized in subcortical, near-thalamic and subthalamic source sites. The near-thalamic dipole was located at significantly different sites in HFO and low-frequency data. CONCLUSIONS: The cortical HFO source constellation points to a 'precortical' source in terminals of thalamocortical fibers and a second intracortical HFO origin. Furthermore, HFOs are also generated at subcortical and even subthalamic sites. Near-thalamic, the HFO and low-frequency signals are generated or modulated by different neuron populations involved in the thalamocortical outflow.

Immediate cortical reorganization after local anesthetic block of the thumb: source localization of somatosensory evoked potentials in human subjects.

Psychophysical observations after anesthesia of the thumb raise the question whether the functional border between the thumb and the index is functionally distinct. We present a source localization study using equivalent current dipole modeling of somatosensory evoked potentials (SEPs) following mechanical air-puff stimulation of the first, second and third digits before and during anesthesia of the thumb. Source reconstruction was based on 96-channel SEP recordings. During anesthesia of the thumb the distance between the cortical representation of the thumb and the second and third digits immediately decreased. This indicates a shift of the cortical representation of the second and third digits towards the deafferented area of the anesthetized thumb. Thus, the present results did not confirm the hypothesis of a functional border of the cortical representation between thumb and index finger in this particular task.

Spatiotemporal imaging of electrical activity related to attention to somatosensory stimulation.

The aim of the present study was to localize the effects of spatial attention on somatosensory stimulation in EEG. Median and tibial nerve were stimulated at all four limbs in a random order. Subjects were instructed to count the events on either the right median or the right tibial nerve. Attention-induced changes in the somatosensory evoked potentials (SEP) were revealed by subtracting the median nerve SEPs recorded while subjects attended to stimuli applied to the tibial nerve from those obtained during attention to the stimulated hand. In a current density reconstruction approach source maxima in the time range from 30 to 260 ms after median nerve stimulation were localized and the time courses of activation were elaborated by dipole modeling. Six regions were identified which contribute significant source activity related to selective spatial attention: contralateral postcentral gyrus (Brodman area (BA) 3), contralateral mesial frontal gyrus (BA 6), right posterior parietal cortex (BA 7), anterior cingulate gyrus (BA 32), and bilateral middle temporal gyrus (BA 21). Activation started at the right posterior parietal cortex, followed by the contralateral middle temporal gyrus, probably representing SII activity, and the middle frontal and anterior cingulate gyrus. Similar regions of source activation were revealed by tibial nerve SEP, but the effect was less pronounced and restricted almost entirely to activation of the contralateral postcentral gyrus (BA 3), anterior cingulate gyrus (BA 32), and ipsilateral middle temporal gyrus (BA 21). Our data provide evidence for a spatially separated frontal generator within the anterior cingulum, dependent on selective attention in the somatosensory modality.

Spatio-temporal source imaging reveals subcomponents of the human auditory mismatch negativity in the cingulum and right inferior temporal gyrus.

We investigated the generators of the mismatch negativity by means of spatio-temporal source imaging on the basis of 64-channel electroencephalography data in order to study the time course and localization of proposed frontal sources. Results indicate that there are additional generators located both within the anterior cingulate gyrus and in the right inferior temporal gyrus, clearly separated from the supratemporal generators in space and time course. The cingulate generator is activated later than the temporal ones, which supports the hypothesis of a frontally located mechanism of involuntary switching of attention triggered by the temporal change detection system. Evidence for an additional right inferior temporal generator supports the hypothesis of right hemispheric dominance in early sound discrimination.

Source reconstruction of mesial-temporal epileptiform activity: comparison of inverse techniques.

PURPOSE: To evaluate whether advanced source reconstruction such as current density reconstruction (CDR) provides additional hints for clinical presurgical evaluation, different source reconstruction techniques with idealized spherical as well as realistically shaped head models (boundary element method, BEM) were applied on interictal and ictal epileptiform activity in presurgical evaluated patients with temporal lobe epilepsy. It is discussed whether CDR and BEM give additional information for presurgical evaluation compared to "conventional" strategies, such as single moving, and spatio-temporal dipole modeling with spherical head models. METHODS: A variety of source reconstruction procedures were applied to the data of five patients with pharmacoresistent temporal lobe epilepsy with probable mesial origin: (1) single-moving dipole in a spherical head model and (2) in BEM, (3) spatio-temporal dipole modeling in a spherical head model and (4) in BEM; and (5) deconvolution with fixed locations and orientations and (6) with cortically constrained L1-norm CDR in BEM. In addition, simulated sources of temporal lobe origin were calculated in each subject with CDR to prove the basic feasibility of this technique in the particular application. RESULTS: Source activity was correctly localized within the affected temporal lobe by all source reconstruction techniques used. Neither single moving dipole, spatio-temporal modeling, nor CDR was able to localize sources at a sublobar level. In the case of two sources, single moving dipole solutions showed changes in dipole orientation in time and spatio-temporal modeling separated two sources, whereas CDR at the peak latency failed to distinguish among different origins. BEM enhanced localization accuracy. CONCLUSION: There was no advantage of using CDR. Single moving dipole as well as spatio-temporal dipole modeling in BEM leads to more precise localization within the individual anatomy and provides a simple algorithm, which is capable of indicating both the time course and the number of sources.

Sleep stage dependant changes of the high-frequency part of the somatosensory evoked potentials at the thalamus and cortex.

OBJECTIVES: It is known that the high-frequency oscillations (above 400 Hz) of the somatosensory evoked potentials (SEPs) diminish during sleep while the N20 persists (Neurology 38 (1988) 64; Electroenceph clin Neurophysiol 70 (1988) 126; Electroenceph clin Neurophysiol 100 (1996) 189). We investigated possible differential effects of sleep on the 600 Hz SEPs at the thalamus and cortex. METHODS: SEPs from 10 subjects were recorded using 64 channels following electric stimulation at the wrist during awake state and sleep stages II, IV and REM. Dipole source analysis was applied to separate brain-stem, thalamic and cortical activity in the low-frequency (20-450 Hz) and the high-frequency (450-750 Hz) part of the signal. RESULTS: The low-frequency SEPs showed a non-significant increase of the latency of the N20 and a bifid change of the waveform in 3 subjects. The high-frequency SEPs showed a significant decrease of their amplitude at the level of the thalamus and cortex but not at the brain-stem. This decrease in amplitude at the thalamus and cortex were significantly correlated. There was no effect on the latency of the signal. In addition, at the cortex, differential effects on early and late parts of the 600 Hz oscillations were found by time-frequency analysis using a wavelet transformation. CONCLUSIONS: Sleep dependent decrease of the high-frequency SEPs were first observed at the thalamus pointing to the known function of the reticular thalamic nucleus regulating arousal. The results presented here provide further evidence for a thalamic origin of the 600 Hz oscillations. In addition, on the basis of the differential effects on early (up to the N20 peak) and late (between 20 and 25 ms) parts of the signal, at least one intracortical generator of these oscillations is proposed. In general, the high-frequency SEPs (600 Hz oscillations) are supposed to reflect activity of a somatosensory arousal system.

Thalamic and cortical high-frequency (600 Hz) somatosensory-evoked potential (SEP) components are modulated by slight arousal changes in awake subjects.

Human somatosensory-evoked potentials (SEP) recorded at the scalp after conventional electrical median-nerve stimulation contain a low-amplitude (<500 nV), high-frequency (approximately 600 Hz) burst of repetitive wavelets, which are superimposed onto the primary cortical response N20. Previous electroencephalographic (EEG) studies have shown: (1) that these wavelets are generated near the hand area of the primary somatosensory cortex and in deep fibers of thalamocortical afferences; and (2) that only the 600-Hz burst, but not the N20 is decreased during sleep. Since the thalamus is involved in regulating both, selective attention and arousal, the present study aimed at characterizing the effects of focused attention and slight arousal changes on the 600-Hz oscillations. A dipole-source analysis of 64-channel SEP recordings after electric right-median-nerve stimulation allowed the comparison of brainstem, thalamic, and two cortical (one tangential, one radial) source activities in ten awake human subjects under two slightly different arousal states (eyes open vs. eyes closed), each tested for three conditions of focused attention (directed towards rare acoustic and right- or left-hand somatosensory target stimuli). While the N20 was not modified at all, the source strength of the high-frequency wavelet burst was significantly increased for eyes opened versus eyes closed, at the thalamic source site as well as for the tangentially oriented cortical source. In contrast, there were no significant differences between conditions with different attentional targets. This evidence for modulatory effects of increased arousal (eyes open) on both thalamic and cortically generated high-frequency SEP activity fits the hypothesis that the 600-Hz SEP burst at least partially represents an arousal-dependent signal generated at the thalamic level and transmitted to the primary somatosensory cortex.

Differential effects of pain and spatial attention on digit representation in the human primary somatosensory cortex.

Reorganization of primary somatosensory cortex subsequent to either reduced or enhanced peripheral input is well established. Recently, plastic changes following arm amputation in humans were shown to correlate with phantom limb pain. This raised the question whether spatial attention and pain may cause cortical reorganization in the absence of deafferentation. Using non-invasive neuroelectric imaging to study the digit representation in the human primary somatosensory cortex, we report a delayed shift of the representation of digits 2-3 due to pain on the digits 4-5, which outlasted the pain by several minutes. In contrast, reorganization during spatial attention was less pronounced, was seen almost immediately and only during the condition. These data indicate that spatial attention and pain without peripheral deafferentation cause cortical reorganization by different mechanisms. The differential time course of reorganizational effects observed at the cortex may be due to modulation of the lemniscal pathways by nociceptive input from the spinal cord dorsal horn.

Dipole-source analysis in a realistic head model in patients with focal epilepsy.

PURPOSE: By the use of three different head models in EEG dipole analysis, we tried to model the origin of interictal and ictal epileptic activity as precisely as possible. Further, as a control, a second evaluation was made by an independent group to control for interindividual reliability of the dipole source analysis. With the realistic head model (CURRY) considering cortex, skull, and skin segmentation, the spike source was located. METHODS: In five patients with mesial temporal epileptogenesis, confirmed by successful epilepsy surgery, the spike source was close to the hippocampus, with a mean distance of the dipole source from the hippocampus of 13.6 mm (range, 9-17.2 mm). In one case the ictal EEG also could be analyzed and resulted in a dipole-source localization comparable to the interictal source. RESULTS: In both head models using either pure cortex segmentation only or a concentric three-shell model, the dipole source was systematically dislocated in a more superior position. Data analysis by a second group with independently chosen EEG samples and identical individual head model resulted in deviations of <5.3 mm. Data analysis using independently selected spikes and independently segmented head models resulted in deviations < or =16.7 mm. CONCLUSIONS: In four cases of extratemporal epileptogenesis, the origin of interictal epileptiform discharges was localized to the suspected primary epileptogenic zone.

Spatial attention modulates the cortical somatosensory representation of the digits in humans.

The topographic organization of the primary somatosensory cortex adapts to alterations of afferent input. Here, electric source imaging was used to show that spatial attention modifies cortical somatosensory representations in humans. The cortical representation of the electrically stimulated digit 2 (resp. digits 2 and 3) of the right hand was more medial along the somatosensory area 3b in subjects who focused attention on digit 4 of the right hand, while it was more lateral when subjects attended digit 4 of the contralateral hand. This effect was very fast since the direction of attention was changed every 6 min. The results indicate that cortical somatosensory representations not only depend on afferent input but vary when spatial attention is directed towards different parts of the body.

N30 and the effect of explorative finger movements: a model of the contribution of the motor cortex to early somatosensory potentials.

OBJECTIVES: The source of the N30 potential in the median nerve somatosensory evoked potentials (SEP) has been previously attributed to a pre-central origin (motor cortex or the supplementary motor area, SMA) or a post-central located generator (somatosensory cortex). This attribution was made from results of lesion studies, the behavior of the potential under pathological conditions, and dipole source localization within spherical volume conductor models. METHODS: The present study applied dipole source localization and current density reconstruction within individual realistically shaped head models to median nerve SEPs obtained during explorative finger movements. RESULTS: The SEPs associated with movement of the stimulated hand showed a minor reduction of the N20 amplitude and a markedly reduced amplitude for the frontal N30 and parietal P27, exhibiting a residual frontal negativity around 25 ms. The brain-stem P14 remained unchanged. Mapping of the different SEPs (movement of the non-stimulated hand minus movement of the stimulated hand) showed a bipolar field pattern with a maximum around 30 ms post-stimulus. In eight out of ten normal subjects, both the N30 and the gN30 (subtraction data) sources resided within the pre-central gyrus, more medially than the post-centrally located N20. Two subjects, in contrast, showed rather post-centrally localized sources in this time range. A model of the cortical SEP sources is introduced, explaining the data with respect to previously described findings of dipole localization, and from lesion studies and the alterations seen in motor diseases. CONCLUSIONS: The results provide evidence for a pre-central N30 generator, predominantly tangentially oriented, located within the motor cortex, while no sources were detected elsewhere. It is suggested that the mechanisms underlying the 'gating' effect during explorative finger movements in the 30 ms time range predominantly arise in the motor cortex.

Evidence for independent thalamic and cortical sources involved in the generation of the visual 40 Hz response in humans.

Multichannel EEG was recorded to study the gamma-band (30-70 Hz) activity phase-locked to visual checkerboard stimulus onset, in grand-average data of 10 subjects and in three additional individuals. Two different approaches for source analysis were applied to reveal source locations and to determine there time course of activity. Two source regions were separated: one in the depth of the brain, suggested to reflect near thalamic activity, and a second at the visual cortex. Analysis of the source activity in time demonstrated significant different frequencies of the deep at 40 Hz and the cortical source at 37 Hz. There was no consistent phase relation between these source activities. These results contradict the thesis of recurrent thalamocortical activity causing gamma-band oscillations involved in the generation of phase-locked visual checkerboard evoked potentials.

Sustained attention modulates the immediate effect of de-afferentation on the cortical representation of the digits: source localization of somatosensory evoked potentials in humans.

Long-term cortical reorganization of the somatotopic arrangement of the digits after alterations of the peripheral input is well established. Studies on the immediate effects of manipulating peripheral input have shown conflicting results indicating that additional factors might modulate cortical reorganization. We present a source localization study using somatosensory evoked potentials (SEP) following electric stimulation of digits one and five before and during anaesthesia of digits two, three and four in 10 normal volunteers. When attention was directed to a stimulus at the dorsal hand, the 3D-distance between digits one and five decreased during as compared to before anaesthesia. In contrast, this distance enlarged when subjects were not attending a particular stimulus. In this condition most subjects focused their attention on the clear sensation of the de-afferented hand region. These results indicate that attention modulates the effect of immediate cortical reorganization of the hand area during partial deafferentation. As an hypothesis: it may be speculated that the sensation of the de-afferentation results in increased synchronized activity of the de-afferented somatosensory cortex and, thus, to its enlarged representation. Conversely, if attention is directed to a different hand region, the representations of the neighboring digits may expand into the de-afferented cortex.

Properties of advanced headmodelling and source reconstruction for the localization of epileptiform activity.

During the last decade multiple work has been done to determine the sources of epileptiform activity by means of dipole source localization based on recordings of the magnetoencephalogram (MEG) or the electroencephalogram (EEG). The actual available advanced volume conductor models and the multiple source reconstruction by regularization may give new impulse to EEG based source analyses in epilepsy patients. This study demonstrates the principal properties of these techniques. We applied two different EEG source reconstruction techniques within different volume conductor models to localize induced spike activity in a selected patient suffering from medically intractable temporal lobe epilepsy: 1) single moving dipole solution in a 3-shell spherical model versus individual head models (boundary-element-model, BEM, and finite-element-model, FEM); 2) a regularization technique for current density reconstructions using both BEM and FEM. When compared to findings of invasive recordings no adequate source locations were derived from the moving dipole solution in both the 3-shell head model and BEM. In contrast, a high congruence of source reconstruction and invasive determination of the focus was obtained using the regularization techniques in both BEM and FEM, indicating the high spatial accuracy of this technique in individual head models.

Fast visual evoked potential input into human area V5.

Studies of the human visual cortex have demonstrated that an area for motion processing (V5) is located in the lateral occipito-temporal cortex. To study the timing of arrival of signals in V5 we recorded multi-channel visual evoked potentials (VEPs) to checkerboard stimuli. We then applied dipole source analysis which was computed on a grand average of 10 subjects, and on five individual subjects, respectively. We demonstrate an early VEP component with onset before 30 ms and with a peak around 45 ms, located in the vicinity of V5. This early component was independent of a second activity, which started around 50 ms and peaked around 70 ms, and was located within the striate cortex (V1). These results provide further evidence for a very fast input to V5 before activation of V1.

Postcentral origin of P22: evidence from source reconstruction in a realistically shaped head model and from a patient with a postcentral lesion.

The source of the radial field of P22 was previously attributed either to the precentral (area 4) or postcentral (area 1) gyrus, on the basis of interpretation of potential maps recorded on the skin or cortex, respectively. The present study used dipole localization within realistically shaped head models and constrained the inverse solution by using the individual cortex and the normals on it, as derived from MR-tomography. In all normal subjects in which a sufficient solution was obtained (6 of 10, goodness of fit above 90%, and relative power of above 94.4% in principal-component analysis) the P22 source resided at the crown of the postcentral gyrus. Further evidence came from a patient with a postcentral lesion (area 1) and loss of P22, while N20-P20 was preserved.

Origin of P16 median nerve SEP component identified by dipole source analysis--subthalamic or within the thalamo-cortical radiation?

Following median nerve stimulation, several monophasic peaks were recorded at the scalp in the 15-18 ms time range. Source analysis, using three different methods, modelled a source near the centre of the head with an orientation towards the activated hemisphere and a peak activity at 16 ms post stimulus. Magnetic recordings detected no signal in this time range, which confirmed a subcortical location of the source. From dipole localization it was not possible to assign the exact origin of the P16 source to either the subthalamic level or the thalamo-cortical radiation, because of the limited spatial resolution at the centre of the spherical head model. An estimate of the conduction velocity of the medial lemniscus pointed towards a subthalamic origin. The P16 source was preserved in two patients with a lesion of the thalamo-cortical radiation and the ventral thalamus. Further evidence for a subthalamic location of P16 was derived from the physical mechanisms generating far-field potentials.

Comparison of realistically shaped boundary-element and spherical head models in source localization of early somatosensory evoked potentials.

Source localizations of early somatosensory evoked potentials and electrical potentials produced by dipoles in the region of the central sulcus were computed using realistically shaped boundary-element head models (BEM) and compared to localizations obtained using 3-shell spherical models. Realistically shaped 3-shell boundary-element-models were constructed on the basis of the individual anatomy obtained from 3D-MR-tomography in 6 subjects. Spherical head models were fitted to the actual locations of the electrodes and to the surface of the heads, respectively. Source locations calculated within the spherical head models differed by an average of 4 mm (range: 2 to 7 mm) with respect to the 3-shell BEM, taking into account the limited accuracy of this model. This mislocation was most prominently due to deeper source locations predicted using a spherical head model and caused by incorrect modelling of the geometry of the heads, although sources were located in a favourable region of the heads.